Neural Substrates of Transcutaneous Spinal Cord Stimulation: Neuromodulation across Multiple Segments of the Spinal Cord

Trevor S Barss, Behdad Parhizi, Jane Porter, Vivian K Mushahwar, Trevor S Barss, Behdad Parhizi, Jane Porter, Vivian K Mushahwar

Abstract

Transcutaneous spinal cord stimulation (tSCS) has the potential to promote improved sensorimotor rehabilitation by modulating the circuitry of the spinal cord non-invasively. Little is currently known about how cervical or lumbar tSCS influences the excitability of spinal and corticospinal networks, or whether the synergistic effects of multi-segmental tSCS occur between remote segments of the spinal cord. The aim of this review is to describe the emergence and development of tSCS as a novel method to modulate the spinal cord, while highlighting the effectiveness of tSCS in improving sensorimotor recovery after spinal cord injury. This review underscores the ability of single-site tSCS to alter excitability across multiple segments of the spinal cord, while multiple sites of tSCS converge to facilitate spinal reflex and corticospinal networks. Finally, the potential and current limitations for engaging cervical and lumbar spinal cord networks through tSCS to enhance the effectiveness of rehabilitation interventions are discussed. Further mechanistic work is needed in order to optimize targeted rehabilitation strategies and improve clinical outcomes.

Keywords: Hoffmann (H)-reflex; interlimb coordination; locomotion; motor-evoked potential; neuromodulation; neurophysiology; rehabilitation; spinal cord injury.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Typical tSCS electrode placement: Transcutaneous SCS is commonly delivered via two 2.5 cm round cathodic electrodes placed over the C3–4 and C6–7 (cervical) or T11 and L1 (lumbar) spinous processes. Two 5 × 10 cm rectangular anodic electrodes are placed bilaterally over the iliac crests.
Figure 2
Figure 2
Schematic of networks within the spinal cord that are potentially altered with tSCS: The main figure highlights the ability of tSCS to modulate ongoing motor output through dorsal root afferents that trans-synaptically facilitate motor output by bringing previously inaccessible motor units closer to their threshold, allowing them to contribute to the execution of a desired task. (A) Large-diameter afferents are likely activated and synapse on several types of interneurons that facilitate ongoing motor output. (B) Among these interneurons are propriospinal interneurons, which transmit this input to multiple segments of the spinal cord in order to alter excitability and impact ongoing motor output throughout the cord. Solid lines indicate that transmission remains intact to the point of injury to the spinal cord, while dashed lines indicate that transmission is impaired, and may be facilitated by tSCS. Typically, tSCS is applied in single unmodulated or modulated monophasic or biphasic pulses or trains of pulses.
Figure 3
Figure 3
Experimental setup for investigating the effect of modulated tSCS on cervicolumbar connectivity and corticospinal facilitation: (A) Hoffmann (H-) reflexes were evoked during tSCS via stimulation of the tibial nerve and recorded in the soleus (SOL) muscle. The left leg was held static in an extended position, and stimulation to evoke the H-reflex was delivered with either the left arm held at 0° or during arm cycling. (B) H-reflexes were evoked during tSCS via stimulation of the median nerve and recorded in the flexor carpi radialis (FCR) muscle, while motor evoked potentials (MEPs) were evoked in the contralateral motor cortex and recorded in the FCR muscle, either with the legs held static, or during leg cycling. Responses were evoked during a consistent background contraction of ≈5–10% peak muscle activity at the same position, regardless of condition.
Figure 4
Figure 4
Effects of tSCS on interlimb connectivity are not similar to those of cycling in terms of reciprocal organization: (A) The schematic highlights common spinal segments activated by tSCS, including the cervical (blue) and lumbar (pink) enlargements. The blue arrow indicates that tonic cervical tSCS inhibits lumbar excitability, while the red arrow indicates that lumbar tSCS facilitates cervical excitability in neurologically intact individuals. (B) Spinal reflex excitability as assessed by the H-reflex in the soleus muscle is significantly inhibited in the presence of cervical tSCS [82]. (C) Spinal reflex excitability is similarly reduced in the lower limbs during arm cycling, which is a known condition for altering interlimb connectivity via presynaptic mechanisms [84,90]. (D) Conversely, spinal reflex excitability as assessed by the H-reflex in the FCR muscle is significantly facilitated in the presence of lumbar tSCS [70]. (E) Leg cycling continues to inhibit spinal reflex excitability in the upper limbs. Panels (B–D) adapted from published data in [70,82].
Figure 5
Figure 5
Convergence across multiple spinal segments facilitates spinal and corticospinal excitability: (A) The schematic highlights that simultaneous cervical and lumbar tSCS (yellow) significantly facilitates cervical spinal reflex and corticospinal excitability. (B) Spinal reflex excitability as assessed by the H-reflex in the flexor carpi radialis (FCR) muscle is significantly facilitated in the presence of combined cervical and lumbar tSCS. (C) Similarly, corticospinal excitability as assessed by MEPs in the FCR elicited from the contralateral motor cortex was also significantly facilitated by combined cervical and lumbar tSCS. Panels (B,C) adapted from published data in [69].

References

    1. Balykin M.V., Yakupov R.N., Mashin V.V., Kotova E.Y., Balykin Y.M., Gerasimenko Y.P. The influence of non-invasive electrical stimulation of the spinal cord on the locomotor function of patients presenting with movement disorders of central genesis. Vopr. Kurortol. Fizioter. Lech. Fiz. Kult. 2017;94:4–9. doi: 10.17116/kurort20179444-9.
    1. Inanici F., Samejima S., Gad P., Edgerton V.R., Hofstetter C.P., Moritz C.T. Transcutaneous electrical spinal stimulation promotes long-term recovery of upper extremity function in chronic tetraplegia. IEEE Trans. Neural Syst. Rehabil. Eng. 2018;26:1272–1278. doi: 10.1109/TNSRE.2018.2834339.
    1. Harkema S., Gerasimenko Y., Hodes J., Burdick J., Angeli C., Chen Y., Ferreira C., Willhite A., Rejc E., Grossman R., et al. Effect of Epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: A case study. Lancet. 2011;377:1938–1947. doi: 10.1016/S0140-6736(11)60547-3.
    1. Angeli C.A., Boakye M., Morton R.A., Vogt J., Benton K., Chen Y., Ferreira C.K., Harkema S.J. Recovery of over-ground walking after chronic motor complete spinal cord injury. N. Engl. J. Med. 2018;379:1244–1250. doi: 10.1056/NEJMoa1803588.
    1. Fregni F., Grecco L., Li S., Michel S., Castillo-Saavedra L., Mourdoukoutas A., Bikson M. Transcutaneous spinal stimulation as a therapeutic strategy for spinal cord injury: State of the art. J. Neurorestoratol. 2015;3:73–82. doi: 10.2147/JN.S77813.
    1. Dimitrijević M.R. Residual motor functions in spinal cord injury. Adv. Neurol. 1988;47:138–155.
    1. Courtine G., Roy R.R., Raven J., Hodgson J., Mckay H., Yang H., Zhong H., Tuszynski M.H., Edgerton V.R. Performance of locomotion and foot grasping following a unilateral thoracic corticospinal tract lesion in monkeys (Macaca mulatta) Brain. 2005;128:2338–2358. doi: 10.1093/brain/awh604.
    1. Friedli L., Rosenzweig E.S., Barraud Q., Schubert M., Dominici N., Awai L., Nielson J.L., Musienko P., Nout-Lomas Y., Zhong H., et al. Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates. Sci. Transl. Med. 2015;7:302ra134. doi: 10.1126/scitranslmed.aac5811.
    1. Rosenzweig E.S., Courtine G., Jindrich D.L., Brock J.H., Ferguson A.R., Strand S.C., Nout Y.S., Roy R.R., Miller D.M., Beattie M.S., et al. Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nat. Neurosci. 2010;13:1505–1512. doi: 10.1038/nn.2691.
    1. Courtine G., Song B., Roy R.R., Zhong H., Herrmann J.E., Ao Y., Qi J., Edgerton V.R., Sofroniew M.V. Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Nat. Med. 2008;14:69–74. doi: 10.1038/nm1682.
    1. Gerasimenko Y., Musienko P., Bogacheva I., Moshonkina T., Savochin A., Lavrov I., Roy R.R., Edgerton V.R. Propriospinal bypass of the serotonergic system that can facilitate stepping. J. Neurosci. 2009;29:5681–5689. doi: 10.1523/JNEUROSCI.6058-08.2009.
    1. Asboth L., Friedli L., Beauparlant J., Martinez-Gonzalez C., Anil S., Rey E., Baud L., Pidpruzhnykova G., Anderson M.A., Shkorbatova P., et al. Cortico-reticulo-spinal circuit reorganization enables functional recovery after severe spinal cord contusion. Nat. Neurosci. 2018;21:576–588. doi: 10.1038/s41593-018-0093-5.
    1. Mayr W., Krenn M., Dimitrijevic M.R. Epidural and transcutaneous spinal electrical stimulation for restoration of movement after incomplete and complete spinal cord injury. Curr. Opin. Neurol. 2016;29:721–726. doi: 10.1097/WCO.0000000000000382.
    1. Formento E., Minassian K., Wagner F., Mignardot J.B., Le Goff-Mignardot C.G., Rowald A., Bloch J., Micera S., Capogrosso M., Courtine G. Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury. Nat. Neurosci. 2018;21:1728–1741. doi: 10.1038/s41593-018-0262-6.
    1. Herman R., He J., D’Luzansky S., Willis W., Dilli S. Spinal cord stimulation facilitates functional walking in a chronic, incomplete spinal cord injured. Spinal Cord. 2002;40:65–68. doi: 10.1038/sj.sc.3101263.
    1. Wagner F.B., Mignardot J.B., Le Goff-Mignardot C.G., Demesmaeker R., Komi S., Capogrosso M., Rowald A., Seáñez I., Caban M., Pirondini E., et al. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018;563:65–93. doi: 10.1038/s41586-018-0649-2.
    1. Kou J., Cai M., Xie F., Wang Y., Wang N., Xu M. Complex Electrical Stimulation Systems in Motor Function Rehabilitation after Spinal Cord Injury. Hindawi. 2021;2021:2214762. doi: 10.1155/2021/2214762.
    1. Gill M.L., Grahn P.J., Calvert J.S., Linde M.B., Lavrov I.A., Strommen J.A., Beck L.A., Sayenko D.G., Van Straaten M.G., Drubach D.I., et al. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat. Med. 2018;24:1677–1682. doi: 10.1038/s41591-018-0175-7.
    1. Courtine G., Gerasimenko Y., Van Den Brand R., Yew A., Zhong H., Song B., Ao Y., Ichiyama R.M., Lavrov I., Roy R.R., et al. Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat. Neurosci. 2009;12:1333–1342. doi: 10.1038/nn.2401.
    1. Angeli C.A., Edgerton V.R., Gerasimenko Y.P., Harkema S.J. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014;137:1394–1409. doi: 10.1093/brain/awu038.
    1. García A.M., Serrano-Muñoz D., Taylor J., Avendaño-Coy J., Gómez-Soriano J. Transcutaneous Spinal Cord Stimulation and Motor Rehabilitation in Spinal Cord Injury: A Systematic Review. Neurorehabil. Neural Repair. 2020;34:3–12. doi: 10.1177/1545968319893298.
    1. Gerasimenko Y., Gorodnichev R., Moshonkina T., Sayenko D., Gad P., Edgerton V.R. Transcutaneous electrical spinal-cord stimulation in humans HHS Public Access. Ann. Phys. Rehabil. Med. 2015;58:225–231. doi: 10.1016/j.rehab.2015.05.003.
    1. Martin R. Utility and Feasibility of Transcutaneous Spinal Cord Stimulation for Patients with Incomplete SCI in Therapeutic Settings: A Review of Topic. Front. Rehabil. Sci. 2021;2:724003. doi: 10.3389/fresc.2021.724003.
    1. Hofstoetter U.S., Freundl B., Binder H., Minassian K. Common neural structures activated by epidural and transcutaneous lumbar spinal cord stimulation: Elicitation of posterior root-muscle reflexes. PLoS ONE. 2018;13:e0192013. doi: 10.1371/journal.pone.0192013.
    1. Ladenbauer J., Minassian K., Hofstoetter U.S., Dimitrijevic M.R., Rattay F. Stimulation of the human lumbar spinal cord with implanted and surface electrodes: A computer simulation study. IEEE Trans. Neural Syst. Rehabil. Eng. 2010;18:637–645. doi: 10.1109/TNSRE.2010.2054112.
    1. Danner S.M., Hofstoetter U.S., Ladenbauer J., Rattay F., Minassian K. Can the Human Lumbar Posterior Columns Be Stimulated by Transcutaneous Spinal Cord Stimulation? A Modeling Study. Artif. Organs. 2011;35:257–262. doi: 10.1111/j.1525-1594.2011.01213.x.
    1. Gad P., Lee S., Terrafranca N., Zhong H., Turner A., Gerasimenko Y., Edgerton V.R. Non-invasive activation of cervical spinal networks after severe paralysis. J. Neurotrauma. 2018;35:2145–2158. doi: 10.1089/neu.2017.5461.
    1. Zheng Y., Hu X. Elicited upper limb motions through transcutaneous cervical spinal cord stimulation. J. Neural Eng. 2020;17:036001. doi: 10.1088/1741-2552/ab8f6f.
    1. Inanici F., Brighton L.N., Samejima S., Hofstetter C.P., Moritz C.T. Transcutaneous Spinal Cord Stimulation Restores Hand and Arm Function after Spinal Cord Injury. IEEE Trans. Neural Syst. Rehabil. Eng. 2021;29:310–319. doi: 10.1109/TNSRE.2021.3049133.
    1. Gerasimenko Y.P., Lu D.C., Modaber M., Zdunowski S., Gad P., Sayenko D.G., Morikawa E., Haakana P., Ferguson A.R., Roy R.R., et al. Noninvasive Reactivation of Motor Descending Control after Paralysis. J. Neurotrauma. 2015;32:1968–1980. doi: 10.1089/neu.2015.4008.
    1. Solopova I.A., Sukhotina I.A., Zhvansky D.S., Ikoeva G.A., Vissarionov S.V., Baindurashvili A.G., Edgerton V.R., Gerasimenko Y.P., Moshonkina T.R. Effects of spinal cord stimulation on motor functions in children with cerebral palsy. Neurosci. Lett. 2017;639:192–198. doi: 10.1016/j.neulet.2017.01.003.
    1. McHugh L.V., Miller A.A., Leech K.A., Salorio C., Martin R.H. Feasibility and utility of transcutaneous spinal cord stimulation combined with walking-based therapy for people with motor incomplete spinal cord injury. Spinal Cord Ser. Cases. 2020;6:104. doi: 10.1038/s41394-020-00359-1.
    1. Hofstoetter U.S., Freundl B., Danner S.M., Krenn M.J., Mayr W. Transcutaneous Spinal Cord Stimulation Induces Temporary Attenuation of Spasticity in Individuals with Spinal Cord Injury. J. Neurotrauma. 2020;493:481–493. doi: 10.1089/neu.2019.6588.
    1. Madhavan S., Hofstoetter U., Estes S.P., Iddings J.A., Field-Fote E.C. Priming neural circuits to Modulate spinal reflex excitability. Front. Neurol. 2017;8:17. doi: 10.3389/fneur.2017.00017.
    1. Cogiamanian F., Ardolino G., Vergari M., Ferrucci R., Ciocca M., Scelzo E., Barbieri S., Priori A. Transcutaneous Spinal Direct Current Stimulation. Front. Psychiatry. 2012;3:63. doi: 10.3389/fpsyt.2012.00063.
    1. Powell E.S., Carrico C., Salyers E., Westgate P.M., Sawaki L. The effect of transcutaneous spinal direct current stimulation on corticospinal excitability in chronic incomplete spinal cord injury. NeuroRehabilitation. 2018;43:125–134. doi: 10.3233/NRE-172369.
    1. Taylor C., McHugh C., Mockler D., Minogue C., Reilly R.B., Fleming N. Transcutaneous spinal cord stimulation and motor responses in individuals with spinal cord injury: A methodological review. PLoS ONE. 2021;16:e0260166. doi: 10.1371/journal.pone.0260166.
    1. Mushahwar V.K., Horch K.W. Proposed specifications for a lumbar spinal cord electrode array for control of lower extremities in paraplegia. IEEE Trans. Rehabil. Eng. 1997;5:237–243. doi: 10.1109/86.623015.
    1. Mushahwar V.K., Jacobs P.L., Normann R.A., Triolo R.J., Kleitman N. New functional electrical stimulation approaches to standing and walking. J. Neural Eng. 2007;4:S181–S197. doi: 10.1088/1741-2560/4/3/S05.
    1. Shealy C.N., Mortimer J.T., Reswick J.B. Electrical Inhibition of Pain by Stimulation of the Dorsal Columns: Preliminary Clinical Report. [(accessed on 19 November 2020)]; Available online:
    1. Cook A.W., Weinstein S.P. Chronic dorsal column stimulation in multiple sclerosis. Preliminary report. N. Y. State J. Med. 1973;73:2868–2872.
    1. Richardson R.R., Cerullo L.J., McLone D.G., Gutierrez F.A., Lewis V. Percutaneous epidural neurostimulation in modulation of paraplegic spasticity—Six case reports. Acta Neurochir. 1979;49:235–243. doi: 10.1007/BF01808963.
    1. Richardson R.R., McLone D.G. Percutaneous epidural neurostimulation for paraplegic spasticity. Surg. Neurol. 1978;9:153–155.
    1. Pinter M.M., Gerstenbrand F., Dimitrijevic M.R. Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 3. Control Of spasticity. Spinal Cord. 2000;38:524–531. doi: 10.1038/sj.sc.3101040.
    1. Andersson O., Forssberg H., Grillner S., Lindquist M. Phasic gain control of the transmission in cutaneous reflex pathways to motoneurones during “fictive” locomotion. Brain Res. 1978;149:503–507. doi: 10.1016/0006-8993(78)90493-6.
    1. Grillner S., Zangger P. On the central generation of locomotion in the low spinal cat. Exp. Brain Res. 1979;34:241–261. doi: 10.1007/BF00235671.
    1. Huang H., He J., Herman R., Carhart M.R. Modulation effects of epidural spinal cord stimulation on muscle activities during walking. IEEE Trans. Neural Syst. Rehabil. Eng. 2006;14:14–23. doi: 10.1109/TNSRE.2005.862694.
    1. Carhart M.R., He J., Herman R., D’Luzansky S., Willis W.T. Epidural Spinal-Cord Stimulation Facilitates Recovery of Functional Walking Following Incomplete Spinal-Cord Injury. IEEE Trans. Neural Syst. Rehabil. Eng. 2004;12:32–42. doi: 10.1109/TNSRE.2003.822763.
    1. Rattay F., Minassian K., Dimitrijevic M.R. Epidural electrical stimulation of posterior structures of the human lumbosacral cord: 2. Quantitative analysis by computer modeling. Spinal Cord. 2000;38:473–489. doi: 10.1038/sj.sc.3101039.
    1. De Noordhout A.M., Rothwell J.C., Thompson P.D., Marsden C.D. Percutaneous electrical stimulation of lumbosacral roots in man. Neurosurg. Psychiatry. 1988;51:174–181. doi: 10.1136/jnnp.51.2.174.
    1. Shapkova E. Spinal locomotor capability revealed by electrical stimulation of the lumbar enlargement in paraplegic patients. Prog. Mot. Control. 2004;3:253–289.
    1. Minassian K., Persy I., Rattay F., Dimitrijevic M., Hofer C., Kern H. Posterior root–muscle reflexes elicited by transcutaneous stimulation of the human lumbosacral cord. Muscle Nerve. 2007;35:327–336. doi: 10.1002/mus.20700.
    1. Hofstoetter U., Hofer C., Kern H., Danner S., Mayr W., Dimitrijevic M., Minassian K. Effects of transcutaneous spinal cord stimulation on voluntary locomotor activity in an incomplete spinal cord injured individual. Biomed. Tech. 2013;58:2–3. doi: 10.1515/bmt-2013-4014.
    1. Hofstoetter U.S., McKay W.B., Tansey K.E., Mayr W., Kern H., Minassian K. Modification of spasticity by transcutaneous spinal cord stimulation in individuals with incomplete spinal cord injury. J. Spinal Cord Med. 2014;37:202–211. doi: 10.1179/2045772313Y.0000000149.
    1. Ward A.R., Robertson V.J. Sensory, motor, and pain thresholds for stimulation with medium frequency alternating current. Arch. Phys. Med. Rehabil. 1998;79:273–278. doi: 10.1016/S0003-9993(98)90006-5.
    1. Manson G.A., Calvert J.S., Ling J., Tychhon B., Ali A., Sayenko D.G. The relationship between maximum tolerance and motor activation during transcutaneous spinal stimulation is unaffected by the carrier frequency or vibration. Physiol. Rep. 2020;8:e14397. doi: 10.14814/phy2.14397.
    1. Jensen M.P., Brownstone R.M. Mechanisms of spinal cord stimulation for the treatment of pain: Still in the dark after 50 years. Eur. J. Pain (United Kingdom) 2019;23:652–659. doi: 10.1002/ejp.1336.
    1. Burke D. Clinical uses of H reflexes of upper and lower limb muscles. Clin. Neurophysiol. Pract. 2016;1:9. doi: 10.1016/j.cnp.2016.02.003.
    1. Lavrov I., Gerasimenko Y.P., Ichiyama R.M., Courtine G., Zhong H., Roy R.R., Edgerton V.R. Plasticity of spinal cord reflexes after a complete transection in adult rats: Relationship to stepping ability. J. Neurophysiol. 2006;96:1699–1710. doi: 10.1152/jn.00325.2006.
    1. Wu G., Ringkamp M., Murinson B.B., Pogatzki E.M., Hartke T.V., Weerahandi H.M., Campbell J.N., Griffin J.W., Meyer R.A. Degeneration of myelinated efferent fibers induces spontaneous activity in uninjured C-fiber afferents. J. Neurosci. 2002;22:7746–7753. doi: 10.1523/JNEUROSCI.22-17-07746.2002.
    1. Ahmed S., Yearwood T., De Ridder D., Vanneste S. Burst and high frequency stimulation: Underlying mechanism of action. Expert Rev. Med. Devices. 2018;15:61–70. doi: 10.1080/17434440.2018.1418662.
    1. Arle J.E., Mei L., Carlson K.W., Shils J.L. High-Frequency Stimulation of Dorsal Column Axons: Potential Underlying Mechanism of Paresthesia-Free Neuropathic Pain Relief. Neuromodulation. 2016;19:385–397. doi: 10.1111/ner.12436.
    1. North J.M., Hong K.S.J., Cho P.Y. Clinical Outcomes of 1 kHz Subperception Spinal Cord Stimulation in Implanted Patients with Failed Paresthesia-Based Stimulation: Results of a Prospective Randomized Controlled Trial. Neuromodulation Technol. Neural Interface. 2016;19:731–737. doi: 10.1111/ner.12441.
    1. Chakravarthy K., Richter H., Christo P.J., Williams K., Guan Y. Spinal Cord Stimulation for Treating Chronic Pain: Reviewing Preclinical and Clinical Data on Paresthesia-Free High-Frequency Therapy. Neuromodulation. 2018;21:10–18. doi: 10.1111/ner.12721.
    1. Benavides F.D., Jo H.J., Lundell H., Edgerton V.R., Gerasimenko Y., Perez M.A. Cortical and subcortical effects of transcutaneous spinal cord stimulation in humans with tetraplegia. J. Neurosci. 2020;40:2633–2643. doi: 10.1523/JNEUROSCI.2374-19.2020.
    1. Sayenko D.G., Rath M., Ferguson A.R., Burdick J.W., Havton L.A., Edgerton V.R., Gerasimenko Y.P. Self-assisted standing enabled by non-invasive spinal stimulation after spinal cord injury. J. Neurotrauma. 2019;36:1435–1450. doi: 10.1089/neu.2018.5956.
    1. Milosevic M., Masugi Y., Sasaki A., Sayenko D.G., Nakazawa K. On the reflex mechanisms of cervical transcutaneous spinal cord stimulation in human subjects. J. Neurophysiol. 2019;121:1672–1679. doi: 10.1152/jn.00802.2018.
    1. Sayenko D.G., Angeli C., Harkema S.J., Reggie Edgerton V., Gerasimenko Y.P. Neuromodulation of evoked muscle potentials induced by epidural spinal-cord stimulation in paralyzed individuals. J. Neurophysiol. 2014;111:1088–1099. doi: 10.1152/jn.00489.2013.
    1. Parhizi B., Barss T.S., Mushahwar V.K. Simultaneous Cervical and Lumbar Spinal Cord Stimulation Induces Facilitation of both Spinal and Corticospinal Circuitry in Humans. Front. Neurosci. 2021;15:379. doi: 10.3389/fnins.2021.615103.
    1. Al’joboori Y., Hannah R., Lenham F., Borgas P., Kremers C.J.P., Bunday K.L., Rothwell J., Duffell L.D. The Immediate and Short-Term Effects of Transcutaneous Spinal Cord Stimulation and Peripheral Nerve Stimulation on Corticospinal Excitability. Front. Neurosci. 2021;15:749042. doi: 10.3389/fnins.2021.749042.
    1. Sasaki A., de Freitas R.M., Sayenko D.G., Masugi Y., Nomura T., Nakazawa K., Milosevic M. Low-intensity and short-duration continuous cervical transcutaneous spinal cord stimulation intervention does not prime the corticospinal and spinal reflex pathways in able-bodied subjects. J. Clin. Med. 2021;10:3633. doi: 10.3390/jcm10163633.
    1. Macefield G., Gandevia S.C., Burke D. Conduction velocities of muscle and cutaneous afferents in the upper and lower limbs of human subjects. Brain. 1989;112:1519–1532. doi: 10.1093/brain/112.6.1519.
    1. Rijken N.H.M., Vonhögen L.H., Duysens J., Keijsers N.L.W. The effect of spinal cord stimulation (SCS) on static balance and gait. Neuromodulation. 2013;16:244–250. doi: 10.1111/j.1525-1403.2012.00512.x.
    1. Dubuisson D. Effect of dorsal-column stimulation on gelatinosa and marginal neurons of cat spinal cord. J. Neurosurg. 1989;70:257–265. doi: 10.3171/jns.1989.70.2.0257.
    1. Zehr E.P., Stein R.B. What functions do reflexes serve during human locomotion? Prog. Neurobiol. 1999;58:185–205. doi: 10.1016/S0301-0082(98)00081-1.
    1. Zehr E.P., Barss T.S., Dragert K., Frigon A., Vasudevan E.V., Haridas C., Hundza S., Kaupp C., Klarner T., Klimstra M., et al. Neuromechanical interactions between the limbs during human locomotion: An evolutionary perspective with translation to rehabilitation. Exp. Brain Res. 2016;234:3059–3081. doi: 10.1007/s00221-016-4715-4.
    1. Beekhuizen K.S., Field-Fote E.C. Massed practice versus massed practice with stimulation: Effects on upper extremity function and cortical plasticity in individuals with incomplete cervical spinal cord injury. Neurorehabil. Neural Repair. 2005;19:33–45. doi: 10.1177/1545968305274517.
    1. Duysens J., Pearson K.G. The role of cutaneous afferents from the distal hindlimb in the regulation of the step cycle of thalamic cats. Exp. Brain Res. 1976;24:245–255. doi: 10.1007/BF00235013.
    1. Vallbo Å.B., Hagbarth K.-E. Activity from Skin Percutaneously Mechanoreceptors in Awake Human Recorded Subjects. Exp. Neurol. 1968;289:270–289. doi: 10.1016/0014-4886(68)90041-1.
    1. Guiho T., Baker S.N., Jackson A. Epidural and transcutaneous spinal cord stimulation facilitates descending inputs to upper-limb motoneurons in monkeys. J. Neural Eng. 2021;18:046011. doi: 10.1088/1741-2552/abe358.
    1. Kaneko N., Sasaki A., Masugi Y., Nakazawa K. The Effects of Paired Associative Stimulation with Transcutaneous Spinal Cord Stimulation on Corticospinal Excitability in Multiple Lower-limb Muscles. Neuroscience. 2021;476:45–59. doi: 10.1016/j.neuroscience.2021.08.028.
    1. Barss T.S., Parhizi B., Mushahwar V.K. Transcutaneous spinal cord stimulation of the cervical cord modulates lumbar networks. J. Neurophysiol. 2020;123:158–166. doi: 10.1152/jn.00433.2019.
    1. Ferris D.P., Huang H.J., Kao P.C. Moving the arms to activate the legs. Exerc. Sport Sci. Rev. 2006;34:113–120. doi: 10.1249/00003677-200607000-00005.
    1. Hundza S.R., Zehr E.P. Suppression of soleus H-reflex amplitude is graded with frequency of rhythmic arm cycling. Exp. Brain Res. 2009;193:297–306. doi: 10.1007/s00221-008-1625-0.
    1. Zhou R., Parhizi B., Assh J., Alvarado L., Ogilvie R., Chong S.L., Mushahwar V.K. Effect of cervicolumbar coupling on spinal reflexes during cycling after incomplete spinal cord injury. J. Neurophysiol. 2018;120:3172–3186. doi: 10.1152/jn.00509.2017.
    1. Dietz V. Do human bipeds use quadrupedal coordination? Trends Neurosci. 2002;25:462–467. doi: 10.1016/S0166-2236(02)02229-4.
    1. Zehr E.P., Hundza S.R., Vasudevan E. V The quadrupedal nature of human bipedal locomotion. Exerc. Sport Sci. Rev. 2009;37:102–108. doi: 10.1097/JES.0b013e31819c2ed6.
    1. Frigon A., Collins D.F., Zehr E.P. Effect of rhythmic arm movement on reflexes in the legs: Modulation of soleus H-reflexes and somatosensory conditioning. J. Neurophysiol. 2004;91:1516–1523. doi: 10.1152/jn.00695.2003.
    1. Frigon A. The neural control of interlimb coordination during mammalian locomotion. J. Neurophysiol. 2017;117:2224–2241. doi: 10.1152/jn.00978.2016.
    1. de Ruiter G.C., Hundza S.R., Zehr E.P. Phase-dependent modulation of soleus H-reflex amplitude induced by rhythmic arm cycling. Neurosci. Lett. 2010;475:7–11. doi: 10.1016/j.neulet.2010.03.025.
    1. Gorodnichev R.M., Pivovarova E.A., Pukhov A., Moiseev S.A., Savokhin A.A., Moshonkina T.R., Shcherbakova N.A., Kilimnik V.A., Selionov V.A., Kozlovskaia I.B., et al. Transcutaneous electrical stimulation of the spinal cord: Non-invasive tool for activation of locomotor circuitry in human. Fiziol. Cheloveka. 2012;38:46–56.
    1. Gerasimenko Y., Gorodnichev R., Puhov A., Moshonkina T., Savochin A., Selionov V., Roy R.R., Lu D.C., Edgerton V.R. Initiation and modulation of locomotor circuitry output with multisite transcutaneous electrical stimulation of the spinal cord in noninjured humans. J. Neurophysiol. 2015;113:834–842. doi: 10.1152/jn.00609.2014.
    1. Sayenko D.G., Atkinson D.A., Floyd T.C., Gorodnichev R.M., Moshonkina T.R., Harkema S.J., Edgerton V.R., Gerasimenko Y.P. Effects of paired transcutaneous electrical stimulation delivered at single and dual sites over lumbosacral spinal cord. Neurosci. Lett. 2015;609:229–234. doi: 10.1016/j.neulet.2015.10.005.
    1. Rothwell J. Control of Human Voluntary Movement. 2nd ed. Chapman & Hall; London, UK: 1994.
    1. Yamaguchi T. Descending pathways eliciting forelimb stepping in the lateral funiculus: Experimental studies with stimulation and lesion of the cervical cord in decerebrate cats. Brain Res. 1986;379:125–136. doi: 10.1016/0006-8993(86)90264-7.
    1. Juvin L., Simmers J., Morin D. Propriospinal circuitry underlying interlimb coordination in mammalian quadrupedal locomotion. J. Neurosci. 2005;25:6025–6035. doi: 10.1523/JNEUROSCI.0696-05.2005.
    1. Juvin L., Le Gal J.-P., Simmers J., Morin D. Cervicolumbar coordination in mammalian quadrupedal locomotion: Role of spinal thoracic circuitry and limb sensory inputs. J. Neurosci. 2012;32:953–965. doi: 10.1523/JNEUROSCI.4640-11.2012.
    1. Zhou R., Alvarado L., Ogilvie R., Chong S.L., Shaw O., Mushahwar V.K. Non-gait-specific intervention for the rehabilitation of walking after SCI: Role of the arms. J. Neurophysiol. 2018;119:2194–2211. doi: 10.1152/jn.00569.2017.
    1. Klarner T., Barss T.S., Sun Y., Kaupp C., Loadman P.M., Zehr E.P. Exploiting Interlimb Arm and Leg Connections for Walking Rehabilitation: A Training Intervention in Stroke. Neural Plast. 2016;2016:1517968. doi: 10.1155/2016/1517968.
    1. Klarner T., Barss T., Sun Y., Kaupp C., Loadman P., Zehr E. Long-Term Plasticity in Reflex Excitability Induced by Five Weeks of Arm and Leg Cycling Training after Stroke. Brain Sci. 2016;6:54. doi: 10.3390/brainsci6040054.
    1. Kaupp C., Pearcey G.E.P., Klarner T., Sun Y., Cullen H., Barss T.S., Zehr E.P. Rhythmic arm cycling training improves walking and neurophysiological integrity in chronic stroke: The arms can give legs a helping hand in rehabilitation. J. Neurophysiol. 2018;119:1095–1112. doi: 10.1152/jn.00570.2017.
    1. Robertson J.V.G., Roby-Brami A. The trunk as a part of the kinematic chain for reaching movements in healthy subjects and hemiparetic patients. Brain Res. 2011;1382:137–146. doi: 10.1016/j.brainres.2011.01.043.
    1. Cetisli Korkmaz N., Can Akman T., Kilavuz Oren G., Bir L.S. Trunk control: The essence for upper limb functionality in patients with multiple sclerosis. Mult. Scler. Relat. Disord. 2018;24:101–106. doi: 10.1016/j.msard.2018.06.013.
    1. Rath M., Vette A.H., Ramasubramaniam S., Li K., Burdick J., Edgerton V.R., Gerasimenko Y.P., Sayenko D.G. Trunk Stability Enabled by Noninvasive Spinal Electrical Stimulation after Spinal Cord Injury. J. Neurotrauma. 2018;35:2540–2553. doi: 10.1089/neu.2017.5584.
    1. Gad P., Gerasimenko Y., Zdunowski S., Turner A., Sayenko D., Lu D.C., Edgerton V.R. Weight bearing over-ground stepping in an exoskeleton with non-invasive spinal cord neuromodulation after motor complete paraplegia. Front. Neurosci. 2017;11:333. doi: 10.3389/fnins.2017.00333.
    1. Estes S., Zarkou A., Hope J.M., Suri C., Field-Fote E.C. Combined transcutaneous spinal stimulation and locomotor training to improve walking function and reduce spasticity in subacute spinal cord injury: A randomized study of clinical feasibility and efficacy. J. Clin. Med. 2021;10:1167. doi: 10.3390/jcm10061167.
    1. Wu Y.K., Levine J.M., Wecht J.R., Maher M.T., LiMonta J.M., Saeed S., Santiago T.M., Bailey E., Kastuar S., Guber K.S., et al. Posteroanterior cervical transcutaneous spinal stimulation targets ventral and dorsal nerve roots. Clin. Neurophysiol. 2020;131:451–460. doi: 10.1016/j.clinph.2019.11.056.
    1. Parhizi B., Barss T.S., Mushahwar V.K. Alteration of H-reflex and MEP amplitude in the flexor carpi radialis muscle with transcutaneous spinal cord stimulation during static and leg cycling tasks in neurologically intact male and female humans. Front. Neurosci. 2021;15:379. doi: 10.34945/F5B59T.

Source: PubMed

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